Grants-in-aid of research RECIPIENTS

Crohn’s and Colitis Canada's Grants-in-Aid of Research program supports Canadian inflammatory bowel disease (IBD) research. The intention of the program is to help advance prevention, treatments, health policy, and to ultimately move us closer to discovering cures for Crohn's disease and ulcerative colitis. These grants support Canadian research projects which have a defined objective and are conducted by an investigator who is either working alone or in collaboration with others. The grants are awarded for up to three years at a maximum of $125,000 per year.

The selection process for the Grants-in-Aid of Research competition is very competitive as each research proposal submitted by either a Canadian researcher or healthcare professional is thoroughly reviewed by a Grant Review Panel comprised of scientific experts and lay persons. The Grant Review Panel scores and ranks the submitted applications based on merit and relevance to the patient community.

Please find below the 2017 recipients of the Grants-in-Aid of Research.

Blunting complex immune responses like those leading to inflammatory bowel disease (IBD) without compromising the ability of our immune system to protect us against infections and cancer is a long-sought after, but daunting goal. Dr. Santamaria’s project is founded on the discovery of a new paradigm in the treatment of autoimmune diseases (caused by the white blood cells of the immune system), specifically the development of a ‘nanomedicine’ (a new type of drug composed of very tiny particles) that can cure several different autoimmune diseases in mice by expanding disease-specific 'regulatory' white blood cells. These regulatory white blood cells put the brakes on the disease-causing autoimmune attack by suppressing the white blood cell of the immune system responsible for orchestrating disease-causing immune responses (the so-called “antigen-presenting cells”). Since the regulatory white blood cells expanded by the developed nanomedicines selectively target the antigen-presenting cells orchestrating a specific disease, they cannot cause generalized suppression of the immune system. Human IBD is the result of a dysregulated immune response to gut bacteria. Dr. Santamaria has discovered that regulatory white blood cells targeting proteins expressed by gut bacteria can reset this balance and protect mice from colitis.

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that are characterized by chronic inflammation in specific regions of the gastrointestinal tract, leading to extensive tissue damage and alterations in overall gut function. While some patients with IBD can be managed by existing therapies, a significant number of patients with CD and UC become unresponsive to drugs, and manifest with severe disease complications often requiring surgical intervention. Fibrosis represents a frequent complication of both CD and UC. The most severe phenotype, in which fibrosis leads to intestinal obstruction, occurs in 30-50% of CD patients within 10 years of disease onset, with 50-60% of patients requiring surgery within 20 years of diagnosis. While underappreciated in UC patients, fibrosis also leads to bowel wall stiffening in this subtype of IBD, an effect that manifests clinically in the form of colonic dysmotility and incontinence. Dr. Hirota is trying to understand how the pregnane X receptor (PXR), a sensor for chemicals of bacterial and environmental origin, regulates key pathways/mechanisms thought to contribute to intestinal fibrosis. Mutations in the PXR gene are associated with IBD, but its role in fibrosis has not been studied. In the long term, Dr. Hirota seeks to implicate the PXR as a viable target for treating intestinal fibrosis in the context of chronic inflammation.

The rate of IBD in Canada is among the highest in the world with more than a quarter of a million people affected. Various clinical guidelines for IBD have been developed to improve the healthcare provided to IBD patients. However, doctors and patients often have differing opinions of what are the most important goals of treatment. Unfortunately, the patient perspective is not always well-represented in planning healthcare delivery. Dr. Nguyen’s work plans to use a survey technique called discrete choice experiments that has long been used in commercial industries to determine what aspects of healthcare are most important to patients. Importantly, the survey methods allow sampling of a very large group of IBD patients throughout Canada so that the perspectives are representative of the entire country. The results of this study will then compare patient perspectives to that of doctors to see where they really differ. This understanding will improve patient-physician communication. Most importantly the results of this study will help policy makers prioritize IBD-related health initiatives that patients feel are most important.

Dr. Reena Khanna | University of Western Ontario
Co-investigator: Dr. Guangyong Zou
Amount: $131,552.32
Date: 2017-2019Research: Development of a New Endoscopic Score for Crohn’s Disease

Meaningful clinical trial outcomes can only be obtained if the most clinically- and scientifically-relevant measures are used to assess disease activity. Research to evaluate and optimize the outcome measures used in Crohn’s disease (CD) clinical trials is therefore crucial. The main objectives of Dr. Khanna’s work is to: develop a novel index for endoscopic assessment of disease activity in CD using statistical methods; assess alternative methods to score ulcers, since these have been shown to predict a response to treatment; compare the reliability of the current endoscopic indices (SES-CD and CDEIS), and the novel index; and to assess their ability to detect changes in disease activity following treatment. Dr. Khanna expects that a new index that is more reliable and sensitive to detecting change in endoscopic disease activity following treatment will be the end result of the studies proposed in this application.

Many patients with inflammatory bowel disease (IBD) believe that diet impacts their symptoms and disease, but evidenced-based nutrition guidelines are lacking. Although patients blog about diet and many on-line sources of information state that certain diets can improve or exacerbate symptoms, few research studies have found a single dietary factor as being protective or harmful for IBD. Novel dietary approaches for the prevention and management of IBD are urgently needed, so health professionals can provide patients with sound nutrition guidance. Fats are essential nutrients to health and must be consumed for normal development and survival. Different types of fats have different effects on the body. Dietary fat can impact the inflammation in our intestine, however the role of different types of fats and their impact on IBD remains unclear. Understanding the effects of fat in IBD is important since fat restriction in a patient with IBD could be harmful to their health and nutritional status. This proposal will examine the effects of dietary fats on colitis both in isolation from each other and in combination as seen in the Mediterranean diet pattern. The Mediterranean diet pattern is widely suggested as an ‘anti-inflammatory’ diet and these properties are believed to be derived from the fat content of the diet. Dr. Gibson’s research shows that monounsaturated and saturated fats combined with fish oil are beneficial in mice with experimental colitis. She will examine the effect of this diet in patients with ulcerative colitis.

The rate of IBD in Canada is among the highest in the world with more than a quarter of a million people affected. Various clinical guidelines for IBD have been developed to improve the healthcare provided to IBD patients. However, doctors and patients often have differing opinions of what are the most important goals of treatment. Unfortunately, the patient perspective is not always well-represented in planning healthcare delivery. Dr. Nguyen’s work plans to use a survey technique called discrete choice experiments that has long been used in commercial industries to determine what aspects of healthcare are most important to patients. Importantly, the survey methods allow sampling of a very large group of IBD patients throughout Canada so that the perspectives are representative of the entire country. The results of this study will then compare patient perspectives to that of doctors to see where they really differ. This understanding will improve patient-physician communication. Most importantly the results of this study will help policy makers prioritize IBD-related health initiatives that patients feel are most important.

Inflammatory bowel disease (IBD) is a childhood illness that can make you feel pain, tired, emotionally upset, and make it hard to see friends or do activities you like. When children become teens they start making more choices about their health. Being a part of making choices about your health can help teens get ready to move to an adult healthcare team. Peer mentoring using the Internet is a new way to help teens with IBD learn to make choices about their health. This study will compare two groups of teens: those who take part in the iPeer2Peer program and those who do not. The iPeer2Peer program matches teens with IBD with a young adult mentor who has learned to manage their IBD well. The teen and their mentor will talk on Skype video calls every week for 20-30 minutes over 3 months. The teens’ ability to take care of themselves, their confidence, their IBD symptoms, their quality of life, and the extra costs of living with IBD, will be measured before, right after and six months after the iPeer2Peer program has taken place. Quality of life will also be measured in mentors before and after they take part in the program. This program is new and different because it uses the Internet to connect teens with mentors. The iPeer2Peer program makes learning to take of yourself easier for young people with IBD. This will make living with IBD easier for teens and may reduce costs to the healthcare system.

Canada has a disproportionately high rate of Crohn’s disease among developed countries, with growing incidence especially among an adolescent population. Knowledge of etiologic routes to Crohn’s disease remains incomplete, however a large body of evidence supports microbes in our gut as active participants in the disease process. For example, inflammation in Crohn’s disease causes expansion of adherent-invasive Escherichia coli (AIEC) bacteria that have pathogen-like characteristics as verified using culture and molecular methods. In previous work, Dr. Coombes developed the first chronic colonization model using human biopsy-isolates of AIEC, allowing him to characterize AIEC-induced inflammation and fibrosis over long periods of time in the host. Leveraging these findings, he is now studying how AIEC persists in the inflamed gut and making novel connections between Crohn's disease risk factors that impact upon how AIEC behaves in the host. Dr. Coombes and his team believe that a quantitative understanding of how Crohn’s disease risk factors interact, through the use of robust pre-clinical models, will lead to the development of targeted interventions to prevent disease in at-risk individuals.

INNOVATIONS IN IBD GRANT RECIPIENTS

The Innovations in IBD Grant is a one-year grant, valued at up to $50,000 that funds novel or innovative approaches to IBD research. The grant stimulates and supports research which may not be encompassed within the boundaries of traditional medical research. This award is open to both Canadian and international applicants.

Similar to the Grants-in-Aid of Research, the selection process for the Innovations in IBD Grant competition is very competitive as each research proposal submitted by either a researcher or healthcare professional is thoroughly reviewed by a Grant Review Panel. Comprised of scientific experts and lay persons, the Grant Review Panel scores and ranks the submitted applications based on merit and relevance to the patient community.

Please find below the 2017 recipients of the Innovations in IBD Grant.

Dr. Humberto Jijon | University of Calgary
Co-investigator: Paul Beck
Amount: $50,000
Date: 2017-2018Research: Development of IgA-SEQ to analyze the human and murine microbiome during colitis

Inflammatory bowel disease is a chronic inflammatory condition of the gut believed to occur in genetically predisposed individuals who are exposed to unknown environmental triggers. In terms of environmental triggers, the microbes that reside in the intestine referred to as the microbiota are likely the most important. The microbiota of each individual is a unique collection of hundreds of different bacterial, viral and fungal species. It seems most likely that individuals with IBD lose tolerance to specific members of their microbiota and thus the microbial perpetuating factors in IBD will vary from individual to individual. Although scientists can look at patterns within the microbiota, it has proven extremely difficult to identify which specific bacterial species drive disease in patients with IBD, likely because different species drive disease in different individuals. Recently however, a group in Yale published a method could allow scientists to use the immune response in IBD to help identify the culprit bacteria that drive inflammation in different individuals. Humans produce antibodies when exposed to bacteria, and these antibodies specifically bind to the surface of these bacteria. Bacteria which exist in a healthy relationship with the host immune system (commensals) may become lightly coated with antibody, whereas bacteria which have lost this relationship and cause inflammation will trigger a strong immune response and ultimately become coated with a greater amount of stronger antibody. In the gut, the primary antibody produced is called IgA, thus looking for bacteria coated with high levels of IgA potentially allows the separation of colitis-causing bacteria (IgA-high) from other innocent bystander bacteria (IgA-low). Once you have separated these bacteria from the rest of the microbiota, the next step is to identify which bacterial species make up this IgA-high group using DNA sequence technologies. This is the process which Dr. Humberto and his team will begin.

Dr. Yasmin Nasser​ | University of Calgary
Amount: $50,000
Date: 2017-2018Research: The role of the microbiome in the chronic and visceral somatic pain in IBD

Inflammatory bowel diseases are chronic, debilitating illnesses. At present, the goal of treatment in IBD is complete healing of intestinal inflammation. However, despite achieving this target, over twenty percent of IBD patients continue to experience chronic abdominal pain, which is a distressing and devastating symptom. Previous research has shown evidence of increased expression of the transient receptor potential vanilloid-1 receptor (TRPV1) in IBD patients with complete intestinal healing; TRPV1 is a key nerve receptor involved in abdominal pain sensation. There is early evidence that disruptions in gut microbes can also change TRPV1 on pain-sensing nerves. Therefore, the goal of Dr. Nasser’s research is to study the role of gut microbes in the development of chronic pain in IBD and the interaction between gut microbes and TRPV1 on pain-sensing nerve by treating an animal model of IBD with chronic pain with antibiotics. Her research may have a broad impact on the health of patients suffering from IBD as it will give us greater understanding into the role of gut microbes in pain sensation. This may in turn lead to new strategies, such as the use of targeted antibiotics against specific gut bacteria, and/or the use of pro- or pre-biotics to treat pain in IBD.

Quick FactFaits en bref

Canada has among the highest incidence rates of Crohn's and colitis in the world.

1 in 140 Canadians lives with Crohn’s or colitis.

Families new to Canada are developing these diseases for the first time.

Incidence of Crohn’s in Canadian kids under 10 has doubled since 1995.